An essential function of a phosphoinositide-specific phospholipase C is relieved by inhibition of a cyclin-dependent protein kinase in the yeast Saccharomyces cerevisiae.
The PLC1 gene product of Saccharomyces cerevisiae is a homolog of the delta isoform of mammalian phosphoinositide-specific phospholipase C (PI-PLC). We found that two genes (SPL1 and SPL2), when overexpressed, can bypass the temperature-sensitive growth defect of a plc1delta cell. SPL1 is identical to the PHO81 gene, which encodes an inhibitor of a cyclin (Pho80p)-dependent protein kinase (Pho85p) complex (Cdk). In addition to overproduction of Pho81p, two other conditions that inactivate this Cdk, a cyclin (pho80delta) mutation and growth on low-phosphate medium, also permitted growth of plc1delta cells at the restrictive temperature. Suppression of the temperature sensitivity of plc1delta cells by pho80delta does not depend upon the Pho4p transcriptional regulator, the only known substrate of the Pho80p/Pho85p Cdk. The second suppressor, SPL2, encodes a small (17-kD) protein that bears similarity to the ankyrin repeat regions present in Pho81p and in other known Cdk inhibitors. Both pho81delta and spl2delta show a synthetic phenotype in combination with plc1delta. Unlike single mutants, plc1delta pho81delta and plc1delta spl2delta double mutants were unable to grow on synthetic complete medium, but were able to grow on rich medium.
Flick
J S
JS
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146, USA. flickjs@ctrvax.vanderbilt.edu
Thorner
J
J
D000595:Amino Acid Sequence; D001483:Base Sequence; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016213:Cyclins / Q000378:metabolism; D004255:Deoxyribodipyrimidine Photo-Lyase / Q000235:genetics; D004791:Enzyme Inhibitors; D004794:Enzyme Repression; D004843:Epistasis, Genetic; D005656:Fungal Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D009154:Mutation; D010710:Phosphates / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D011506:Proteins; D012097:Repressor Proteins; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D012641:Selection, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013489:Suppression, Genetic; D010738:Type C Phospholipases / Q000235:genetics*
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; C066824:PHO80 protein, S cerevisiae; C081227:PHO81 protein, S cerevisiae; D010710:Phosphates; D011506:Proteins; D012097:Repressor Proteins; C111070:SPL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D018844:Cyclin-Dependent Kinases; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; C088014:spore photoproduct lyase; D004255:Deoxyribodipyrimidine Photo-Lyase; D043265:Phosphatidylinositol Diacylglycerol-Lyase